Apparatus for pipetting power

ABSTRACT

The present invention provides apparatus and methods for collecting a plurality of measured quantities of a powdered material and dispensing each of the measured quantities to, for example, a multi-well vessel. Vacuum is used to collect the powdered material and at least one of gravity, a gas push, or a physical push is used to dispense the powdered material. Apparatus and methods of the invention are particularly useful for collection and delivery of powdered materials in high throughput chemical synthesis and biological assay environments where accurate measurement and dispensing of powders is critical.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to apparatus and methods for handlingsmall-particle size solid materials, such as powders, granules, beads,and the like. More specifically, the invention relates to apparatus andmethods for collecting and dispensing powdered materials for highthroughput applications, such as those using multi-well apparatus, as inchemical, biological, and biochemical research.

2. Summary of Related Art

There are many arts that require measurement and dispensing of a definedquantity of a powder. Technological arts such as pharmaceuticalmanufacturing, powder coating, confection manufacturing, powdermetallurgy, cosmetics, spices, and flavorings are some examples.

There is an especially important need for efficient powder measuring anddispensing for arts that use multi-well format vessels such as thoseused in high throughput chemical synthesis, bioassays, and the like. Forexample, in combinatorial chemical synthesis, a measured amount of apowdered reagent or resin is often added to each of a plurality ofreaction wells in, for example, a 96-well format reactor. Withcontinually improving technology, these multi-well reactors (and assayplates) are becoming smaller and smaller, and thus the amount ofpowdered material needed for each well is steadily becoming smaller andsmaller. Therefore, for high throughput applications, there is a needfor apparatus and methods for accurately adding small measured amountsof powdered reagents or resins simultaneously to each of a plurality ofwells.

Another need in the art, for example in commercial combinatorialchemistry efforts, is for more accurate dispensing of moderately smallsized (on the order of grams and/or fractions of grams) amounts of solidresins. For example, a trend in modern combinatorial chemistry is tomake tens to hundreds (or even thousands) of milligrams of a number ofindividual compounds, and to purify the compounds in a high-throughputfashion. In order to control stoichiometries of the correspondingformation reactions, the resins used for the reactions must beaccurately quantitatively dispensed simultaneously to each of aplurality of wells.

There are conventional apparatus that one can employ for retrieving anddelivering small measured amounts of powdered solids. For example, theDryPette® powder pipette (available from Zinsser Analytic of FrankfurtGermany) is capable of collecting a measured volume of a powder andexpelling it. However, this pipette system only handles a single dose ofsolid at one time. In order to deliver a plurality of doses, to forexample a 96-well plate, requires the user to perform 96retrieve-and-dispense operations. As well, there is significant room foruser error (e.g. cross-contamination and/or dispensing to the wrongwell) when pipetting to a multi-well vessel because the wells arearranged contiguously.

There is at least one conventional apparatus for dispensing smallmeasured amounts of powdered reagents or resins simultaneously to eachof a plurality of wells in a multi-well format vessel. The MiniBlockResin Dispenser® (available from Mettler-Toledo Bohdan, Inc. of VernonHills, Ill.) is used to dispense pre-measured amounts of resins andpowders to all wells of a multi-well vessel. This apparatus uses ameasuring plate system, a top plate having a plurality of fixed-volumeholes (each corresponding to each well of a multi-well vessel) slidablyengage-able with a bottom plate. When engaged, the plates form aplurality of fixed volume cavities that must be hand loaded by scrapingresin across the top plate to fill the cavities. Once filled, the bottomplate is removed, and gravity is used to dispense resin from each of theholes and into each corresponding well of a multi-well vessel. To varythe amount of resin measured, the user must choose a top plate withappropriately sized measuring holes.

Although the MiniBlock Resin Dispenser® allows for measurement andaddition of powdered solids to all wells of a multi-well vessel, thereare inherent problems with this approach. For example, since the holesare filled via manual scraping of solid material across a measuringplate, there can be variation in the level of compaction of the solidmaterial in each of the cavities. This leads to variation in the amountof solid added to each well. Additionally, since the cavities are filledfrom the top, the excess powder must be scraped off of the plate eachtime and returned to a bulk supply used for filling the platessuccessively. This is manually intensive and time consuming, aproblematic situation, especially in a high-throughput environment.Finally, in order to fill different wells of a given multi-well vesselwith different amounts of resin, a user would either have to switch outplates during the addition process (using only a portion of each plate'sholes for each measure/dispense operation) or manufacture plates withvarying hole bore, depending on the need. The former scenario presentssignificant cross contamination issues (e.g. when loading a variety ofreagents) and the latter significant up-front time and materialcommitment.

What is needed therefore are apparatus and methods for simultaneouslyand automatically collecting and measuring a plurality of measuredquantities of a powdered material and delivering each measured quantitysimultaneously to a corresponding receiving vessel. Particularlyapparatus that allow such operations for all wells or a subset of wellsof a given multi-well vessel, without manually changing out componentsof the apparatus.

SUMMARY OF THE INVENTION

The present invention provides apparatus and methods for collecting,substantially simultaneously, a plurality of measured quantities of apowdered material and dispensing, substantially simultaneously, each ofthe measured quantities to, for example, a multi-well vessel. Vacuum isused to collect the powdered material and at least one of gravity, a gaspush, or a physical push is used to dispense the powdered material.Apparatus and methods of the invention are particularly useful forcollection and delivery of powdered materials in high throughputchemical synthesis and biological assay environments.

One aspect of the invention is an apparatus for automaticallycollecting, substantially simultaneously, a plurality of measuredquantities of a powdered material and dispensing, substantiallysimultaneously, each of the plurality of measured quantities of thepowdered material. Such apparatus may be characterized by the followingaspects: a plurality of collection cavities, each of the collectioncavities including an inlet for fluid communication therein and a filterconfigured to prevent the powdered material from entering a vacuumsource; said vacuum source connected to each of the plurality ofcollection cavities via the inlet therein; and a control valveconfigured to establish or terminate fluid communication between thevacuum source and each of the plurality of collection cavities. Alsopreferably apparatus of the invention include a plurality of valves forcontrolling fluid communication between at least the vacuum source andall or a sub-set of the plurality of collection cavities.

Preferably the volume of each of the plurality of collection cavities isdynamically adjustable. Also preferably, each of the plurality ofcollection cavities is capable of holding between about 0.005 cm³ and 2cm³ of the powdered material, more preferably between about 0.01 cm³ and1 cm³ of the powdered material, and most preferably between about 0.1cm³ and 0.5 cm³ of the powdered material. Preferably, apparatus of theinvention are capable of collecting each of the measured quantities ofthe powdered material to within about ±0.1 cm³, more preferably towithin about ±0.005 cm³, and most preferably between about ±0.001 cm³.

In a particularly preferred embodiment, the plurality of collectioncavities are configured on a collection member such that when thecollection member is registered with a multi-well vessel, each cavity ofthe plurality of collection cavities is positioned to dispense itscorresponding quantity, of the plurality of measured quantities ofpowdered material, into a corresponding well of the multi-well vessel.Preferably the multi-well vessel includes at least one of an 8-wellformat vessel, a 24-well format vessel, a 96-well format vessel, a384-well format vessel, and a 1536-well format vessel. In a particularlypreferred embodiment, the collection member includes a plurality ofholes, the plurality of holes slidably engage-able with; a plurality ofplungers, each of the plurality of plungers including a tube, open atboth ends, the aforementioned filter affixed at the end (or integral tothe plunger, e.g. if the plunger and filter are made as one piece, e.g.via an injection mold process) of the tube in proximity to the powderedmaterial during collection and the other end of the tube in fluidcommunication with the vacuum source. Thus the “face” of the plunger, isthe end of the tube with the filter affixed to it or the filter definesthe end of the tube (is part of the tube, supra). Additionally, thefilter may be part of an assembly that engages with the tube to form the“plunger.”

Preferably the volume of each collection cavity is defined substantiallyby the volume from the aperture of its corresponding hole to the face ofits corresponding plunger. In preferred embodiments, an adjustmentmechanism is used to dynamically adjust the volume of the collectioncavities prior to or during collection of a powder. Preferably theadjustment mechanism includes at least one of a lead screw, a pneumaticcylinder, and a flexible-membrane. In an alternative embodiment,collection cavity inserts are used to adjust the collection cavityvolume. Such inserts are particularly useful when they include thefilter (e.g. as an assembly) as mentioned above. In one embodiment aninsert that engages with the tube is used, one surface of the insertserving as the plunger face (which comprises the filter).

Most preferably apparatus of the invention include a controller, thecontroller including: a plurality of solenoids for controlling thecontrol valve and the plurality of valves; the vacuum source; a positivepressure source for delivering a positive pressure of a gas; and anassociated logic configured to automatically control the plurality ofsolenoids based on a manual switch control, a pre-programmed algorithm,or both. Preferably the control valve, the plurality of valves, andcombinations thereof are used to control fluid communication betweeneach of the collection cavities, via their respective inlets, and eitherthe vacuum source or the positive pressure source. Apparatus of theinvention can include a hand held collection member wherein thecontroller is a remote controller, as well as fully automated apparatusfor carrying out methods of the invention (infra) without the need formanual manipulation of the collection member.

In a preferred embodiment, apparatus of the invention include a supplybin for holding the powdered material, the supply bin including: apowder compartment sized and shaped to accommodate a supply of thepowdered material and the collection member when collecting the powderedmaterial in the plurality of collection cavities therein; and a squeegeeconfigured to remove at least a portion of the powdered material thatprotrudes beyond the aperture of each of the plurality of collectioncavities, during collection, when the aperture of each of the pluralityof collection cavities and the squeegee are moved across one another.Preferably the supply bin is configured such that the portion of thepowdered material that protrudes beyond the aperture of each of theplurality of collection cavities, after removed by the squeegee, isreturned into the powder compartment or collected in a powder catchcompartment.

Another aspect of the invention is a method of collecting and dispensinga powdered material. Such methods may be characterized by the followingaspects: collecting, substantially simultaneously, a plurality ofmeasured quantities of the powdered material in a plurality ofcollection cavities, wherein each of the plurality of collectioncavities is in fluid communication with, via an inlet within eachcavity, a vacuum source; and dispensing, substantially simultaneously,the plurality of measured quantities of the powdered material byterminating, substantially simultaneously, fluid communication betweeneach of the plurality of collection cavities and the vacuum source whileeach of the plurality of collection cavities is oriented such thatgravity pulls each of the plurality of measured quantities of thepowdered material out of each of the plurality of collection cavities.Preferably each of the plurality of collection cavities includes afilter to substantially prevent the powdered solid from entering theinlet.

In a preferred embodiment, the volume of each of the plurality ofcollection cavities is dynamically adjusted during collection of thepowdered material. Methods of the invention may further include applyinga positive pressure of a gas to each of the collection cavities, via theinlet within each cavity, to facilitate removal of each of the pluralityof measured quantities of the powdered material. Preferably the gasincludes at least one of air and an inert gas.

Preferred methods of the invention include moving a squeegee and theaperture of each of the plurality of collection cavities across eachother, to remove at least a portion of the powdered material thatprotrudes beyond the aperture of each of the plurality of collectioncavities, after collection and before dispensing.

Methods of the invention are particularly suited for apparatus of theinvention as described above. In particular, methods of the inventionmay be carried out using all or a sub-set of the plurality of collectioncavities as described. Particularly preferred methods of the inventioninclude using either a hand-held unit, the hand held unit including theplurality of collection cavities or an automated mechanism. Preferablysuch an automated mechanism is configured to collect the powderedmaterial in all or the sub-set of the plurality of collection cavities,move the aperture of each of the plurality of collection cavities andthe squeegee across one another, and deliver each of the plurality ofmeasured quantities of the powdered solid, via the plurality ofcollection cavities, to a plurality of vessels corresponding to all orthe sub-set of the plurality of collection cavities containing thepowdered material.

These and other more detailed aspects of the invention are describedbelow in relation to the following figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top perspective of a resin handler of the invention.

FIG. 2 is a bottom perspective of the resin handler depicted in FIG. 1.

FIG. 3 is a top view of the resin handler depicted in FIG. 1, indicatingside view cross sections corresponding to FIGS. 4 and 5.

FIG. 4 is a side view cross section of the resin handler as indicated inFIG. 3.

FIG. 4A depicts a detailed portion of the side view cross section of theresin handler in FIG. 4.

FIG. 5 is a side view cross section of the resin handler as indicated inFIG. 3.

FIG. 6 is a top perspective of the resin handler engaged with a 96-wellvessel.

FIG. 7 is a cross section of the resin handler engaged with a 96-wellvessel as indicated in FIG. 6.

FIGS. 8A and 8B depict a supply bin of the invention without and with alid, respectively.

FIG. 9 is a flowchart depicting aspects of a process flow in accordancewith the invention.

DETAILED DESCRIPTION OF THE INVENTION

In the following detailed description of the present invention, numerousspecific embodiments are set forth in order to provide a thoroughunderstanding of the invention. However, as will be apparent to thoseskilled in the art, the present invention may be practiced without thesespecific details or by using alternate elements or processes. In otherinstances well-known processes, procedures and components have not beendescribed in detail so as not to unnecessarily obscure aspects of thepresent invention.

As mentioned, the invention provides apparatus and methods forcollecting, substantially simultaneously, a plurality of measuredquantities of a powdered material and dispensing, substantiallysimultaneously, each of the measured quantities to, for example, amulti-well vessel. Vacuum is used to collect the powdered material andat least one of gravity, a gas push, or a physical push is used todispense the powdered material. Apparatus and methods of the inventionare particularly useful for collection and delivery of powderedmaterials in high throughput chemical synthesis and biological assayenvironments. In the following detailed description of an embodiment ofthe invention, reference numbers are carried through the figures asappropriate. The following is a description of a particularly preferredembodiment of the invention and is not intended to limit the scope ofthe invention.

Definitions

As used in the present specification, the following words and phrasesare generally intended to have the meanings as set forth below, exceptto the extent that the context in which they are used indicatesotherwise.

In this application the term “powder” or “powdered material” is meant tomean small-particle size solid materials, such as powders, granules,beads, and the like. Small-particle size materials generally have anaverage particle diameter on the order of between about 5 μm and 1000μm, although smaller and larger particles are meant to fall within thescope of the invention.

In this application the term “dynamically adjustable” is meant to mean amechanism of an apparatus of the invention that can be adjusted orotherwise controlled without having to change out components or addcomponents to the apparatus that includes the mechanism.

In this application the term “squeegee” is meant to mean a mechanismused to remove a portion of a measured quantity of a powdered materialcollected via a collection cavity. In an exemplary resin handlerdescribed below, a squeegee is described as a mechanical member used toremove (e.g. via drawing the squeegee and a collection member across oneanother) a portion of a measured quantity of a collected powder thatprotrudes beyond the aperture of such a collection cavity. It isunderstood by one skilled in the art that a “squeegee” may also includeother mechanisms for powder removal such as a jet of air (air knife) andthe like. Additionally, removal by a squeegee of the invention mayinclude removal of a portion of a measured quantity of powdered materialfrom within such a collection cavity (from an area within the apertureof the collection cavity).

Resin Handler

FIGS. 1-7 show various views of an exemplary resin handler, 100, of theinvention. Resin handler 100 is used to collect a plurality of measuredquantities of a powdered material and deliver each of the measuredquantities to a corresponding vessel or well of a multi-well vessel.Each individual measured quantity is collected (via vacuum) in, anddispensed from, a collection cavity 107 (see also FIGS. 2 and 4). Inthis example, resin handler 100 is a hand held unit in fluid andelectrical communication with a controller (remote, not shown).Apparatus of the invention require a vacuum source for collectingpowdered materials; however in this example; the controller contains avacuum source, a positive pressure source, electrical solenoids forcontrolling the vacuum and positive pressure sources, etc.

One skilled in the art would understand that resin handlers of theinvention can also be automated units and/or self-contained units withan associated logic for automatically controlling resin handlingfunctions described in this example as hand operations. Such embodimentswill include components (such as robotic arms, tracks, and the like) tomove and otherwise manipulate (for example as described below) a resinhandler similar to resin handler 100.

FIG. 1 shows a top perspective of resin handler 100. Resin handler 100has a collection member 101, which in this case is made from a block ofrigid material. Preferred rigid materials for the collection memberinclude but are not limited to plastics, metals, and the like. Powderedmaterials are often affected by static charge and can thus be hard tohandle. In a particularly preferred embodiment, the collection memberincludes an anti-static material. Preferably the anti-static materialincludes at least one of a plastic, a metal, a glass, and a ceramic.

Referring to FIGS. 2, 4 and 5, collection member 101 has a plurality ofcollection cavities, 107, therein. Each of collection cavities 107 isformed by a combination of a hole in collection member 101 that isslidably engage-able with a plunger 103. FIGS. 4 and 5 cross-sections ofresin handler 100, showing that the volume of collection cavities 107 isdetermined by the relative position (as measured by distance 131) ofplungers 103 within the holes in collection member 101. Preferably eachof the collection cavities is capable of holding between about 0.005 cm³and 2 cm³ of the powdered material, more preferably between about 0.01cm³ and 1 cm³ of the powdered material, and most preferably betweenabout 0.1 cm³ and 0.5 cm³ of the powdered material. Preferably,apparatus of the invention are capable of collecting each of themeasured quantities of the powdered material to within about ±0.1 cm³,more preferably to within about ±0.005 cm³, and most preferably towithin about ±0.001 cm³.

One skilled in the art would understand that the collection member cantake other shapes and configurations depending on the distribution ofthe receiving vessels that are to be used. Preferably the plurality ofcollection cavities are configured on collection member such that whenthe collection member is registered with a multi-well vessel, eachcavity of the plurality of collection cavities is positioned to dispenseits corresponding quantity, of the plurality of measured quantities ofpowdered material, into a corresponding well of the multi-well vessel.Preferably the multi-well vessel includes at least one of an 8-wellformat vessel, a 24-well format vessel, a 96-well format vessel, a384-well format vessel, and a 1536-well format vessel.

In this example, plungers 103 are moved within the holes of collectionmember 101 in unison, however the invention is not limited in this way.Other embodiments of the invention have collection cavities whose volumecan be varied independently. An analogy to this example would includeindependently movable plungers 103, although one skilled in the artwould understand that other mechanisms for volume adjustment areincluded within the scope of the invention.

Preferably, but not necessarily, resin handlers of the invention includesuch dynamic volume adjustment as described above, that is, apparatuswherein no parts of the apparatus need be changed out in order to adjustthe cavity volumes. For example, in an alternative embodiment, aflexible membrane is positioned over a plurality of deformationcavities, the membrane including a plurality of filter elements, eachregistered with a corresponding deformation cavity. For example, themembrane can be perforated to form such filter elements, or the membranecan be made of a material, for example a woven fabric, that serves bothdeformation and filtration functions. A vacuum source applied fromwithin each deformation cavity (i.e. a pressure differential on eitherside of the membrane) serves to warp or deform the membrane into thedeformation cavity and collect a powder into the concave portions of theflexible membrane thus formed. Upon release of vacuum the membranereforms to its original shape (substantially flat) and expels each ofthe individual quantities of collected powder. In one embodiment themembrane deforms to meet with the interior surface of each of theplurality of deformation cavities, thus the cavities define the volumeof powder collected. In another embodiment, the deformation cavitieshave a volume that the deformed membrane is unable to match, that is,the membrane can be variably deformed within each of the plurality ofdeformation cavities (e.g. via variable vacuum to each cavity) to thuscollect various desired quantities of powder rather than beingrestricted to the volume defined by deformation to match the volume ofthe deformation cavities. In a particularly preferred embodiment, asingle member contains the plurality of deformation cavities. In anotherparticularly preferred embodiment vacuum can be applied independently(and variably) to each deformation cavity of the matrix of deformationcavities.

In an alternative embodiment, the flexible membrane is warped ordeformed mechanically, at each desired collection cavity formation area,via mechanical force. Such mechanical force preferably includes apulling force applied via an arm, wire, tube (e.g. used to supply vacuumto form a cavity) or other similar device or combinations thereofaffixed to the membrane. When the pulling force is applied, and forexample in combination with a localized member (for example a perforatedmember between the membrane and a vacuum source) to hold at least aportion of the membrane in its original orientation, a collection cavityis formed in the membrane, at each attachment point of such a mechanicaldevice as the aforementioned. A vacuum is applied via the vacuum sourcein order to fill each collection cavity with powder. Again, upon releaseof vacuum the membrane reforms to its original shape (substantiallyflat) and expels each of the individual quantities of collected powder.By using mechanical force, the function of the vacuum source does notinclude deformation of the membrane, but rather collecting, holding, andoptionally expelling powder. By decoupling the membrane deformationfunction from the vacuum source, flexibility is added to the collectionprocess and devices used for collection.

Again referring to FIGS. 4 and 5, powder is collected in cavities 107via a vacuum source. As depicted, in the face of each plunger 103 servesas a portion of the interior surface of each cavity 107. Referring toFIG. 4A, the face of each plunger 103 includes a filter 133. In thisexample, each of plungers 103 includes a hollow tube that serves as aconduit (see 134) for fluid communication with the vacuum source, and afilter 133 that is part of an insert assembly that engages with eachtube. In this example, the insert assembly and corresponding filter 133travel with the tube as it is moved within its corresponding hole in thecollection member.

Each plunger 103 is attached to, and in fluid communication with, amanifold 105. Manifold 105 is in fluid communication with the vacuum orpositive pressure source (in this example, both in a remote controlleras described above) via fluid communication lines 123. Filter 133substantially prevents powdered material from entering the interior ofplungers 103 (and the vacuum source via manifold 105 and lines 123)during powder collection into cavities 107. Preferably, filter 133 iscapable of excluding particles with an average particle size of betweenabout 1 μm and 1000 μm, more preferably between about 1 μm and 500 μm,and most preferably between about 10 μm and 500 μm. Preferably filtersof the invention include at least one of a semi-rigid screen, a sieve, acollection of micro-tubes, perforated ceramic, perforated plastic,perforated glass, a porous cermet, and a porous metal.

Thus, powder is collected into cavities 107 by application of a vacuumfrom within each of cavities 107. The volume of each of cavities 107 isadjusted by positioning the plungers appropriately within each cavity.Powder is dispensed from cavities 107 by shutting off (via a controlvalve, not shown) fluid communication between the vacuum source and eachof the cavities from which powder is to be dispensed. One skilled in theart would understand that any number of combinations of cavity volumeand all or a sub-set of the collection cavities can be used to bothcollect and dispense the powdered material, and such combinations do notescape the scope of the invention.

Although this exemplary apparatus has both vacuum and positive pressurecapability, the invention need only have a vacuum source and a valve tocut off fluid communication between the vacuum source and the collectioncavities (e.g. via manifold 105). Preferably the vacuum and positivepressure source are capable of providing both high and low vacuum andpressure, respectively. In this example, there are four fluidcommunication lines 123, but depending on the design of manifold 105,theoretically there need only be a single fluid communication line to amanifold of the invention. In this example, a plurality of lines is usedto establish a desirable fluid distribution within manifold 105 specificto particular resin handling applications.

Manifold 105 is attached to a handle 125. Within handle 125 is anelectrical communication line 129 for sending signals to solenoids (inthe controller) for controlling the valves that regulate pressure withinmanifold 105 via a switch, 127, in handle 125. Switch 127 isconveniently thumb-operated while resin handler 100 is held via handle125. In this embodiment, switch 127 has three positions, vacuum, off,and positive pressure. Vacuum is used to draw a powdered material into aselected number (all or a subset) of collection cavities 107 andpositive pressure may be used to push powdered material out of thecavities for dispensing or as a cleaning aide. Preferably a push gas isused, the push gas preferably including at least one of air and an inertgas.

Referring to FIG. 2, each of the collection cavities has a guide, 109,at its aperture. Guide 109 aides in alignment of each collection cavitywith a corresponding well of a multi-well vessel or a correspondingvessel of a plurality of vessels, when the collection member is engagedwith such vessels. Included also in this example, are guides 111 and 113for aiding alignment of collection member 101 with, for example, theupper edges around the perimeter of a 96-well vessel. In this example,there are 96 collection cavities 107, however the invention is notlimited in this way.

FIG. 6 is a perspective of resin handler 100 registered with a 96-wellvessel, 141. Vessel 141 is a multi-well apparatus for chemical andbiological analysis and synthesis, and is described in more detail inU.S. patent application Ser. No. 10/094,253, filed on Mar. 8, 2002,naming David C. Hager, et al as inventors, entitled, “Multi-wellApparatus,” which is incorporated by reference herein for all purposes.As depicted in FIG. 6, when resin handler 100 (more specificallycollection member 101) is registered with vessel 141, guides 111 and 113extend over the topmost outer perimeter of vessel 141. FIG. 7 is across-section of resin handler 100 registered with vessel 141, showingthat guides 109 extend part way into the aperture of wells 143 of vessel141, and thus not only aide in alignment but also ensure delivery ofpowdered material from each cavity into its corresponding well, sinceeach collection cavity is registered with a specific well via itscorresponding guide 109.

Referring to FIG. 2, posts 120 are affixed to collection member 101,passing through holes in the member and into holes through manifold 105and handle 125. The handle and manifold assembly is slidably engage-ablewith posts 120. Springs 119 (refer also to FIGS. 1, 2, and 4-6) areconcentric to posts 120 and provide resistance to movement of the handleand manifold assembly toward collection member 101. Thus, when resinhandler 100 is engaged with a reaction vessel (as depicted in FIGS. 6and 7) and sufficient downward force (to compress springs 119) on handle125 is applied, the handle/manifold assembly slides on posts 120 andpushes plungers 103 to displace material with collection cavities 107. Astop, 145, is used to prohibit movement of the manifold's bottom facebeyond the level of the stop. When such a downward force applied tohandle 125 is released, springs 119 return the handle/manifold assembly(and plungers 103) back to their original position. Thus, thehandle/manifold assembly is capable of sliding bi-directionally alongposts 120. See heavy double-headed arrow in FIG. 7 indicating range ofbi-directional movement.

Thus powdered material is delivered from cavities 107 by one of threemechanisms or combinations thereof: cutting off vacuum (i.e. return toatmospheric pressure followed by gravity pulling the powder out of eachcavity), positive pressure push, and physical displacement via plungers103. Again, apparatus of the invention need only include the firstmechanism, but may include any combination of the three mechanisms.Depending on the powdered material and application, any or all of thesedisplacement mechanisms may be desirable.

Resin handlers of the invention include an adjustment mechanism fordynamically adjusting the volume of the collection cavities. In thisexample, the volume of collection cavities 107 is adjusted viapositioning each plunger 103 within its respective hole in collectionmember 101. Lead screws 117 are affixed to collection member 101 andextend through manifold 105. At the top of each lead screw 117 is anadjustment thumbscrew 115. When thumbscrews 115 are turned in theappropriate direction on the threads (not shown) on lead screw 117, thisapplies downward force (directly opposing the upward force supplied bysprings 119) onto the manifold pushing it along posts 120 towardcollection member 101, thus adjusting the position of plungers 103within their respective holes in the collection member. As mentioned,springs 119 provide sufficient force to maintain a fixed distancebetween the handle/manifold assembly and collection member 101; thisforce can be overcome, for example, by downward force delivered tohandle 125. One skilled in the art would appreciate that automatedcavity volume adjustment mechanisms are also within the scope of theinvention. Preferably the adjustment mechanism includes at least one ofa lead screw, and a pneumatic cylinder.

In this example, the adjustment mechanism includes a graduated cylinder,121, used to demark the position of the bottom face of manifold 105. Asmentioned, the manifold's position, 131 (refer to FIG. 5), relative tocollection member 101, determines the position of each of plungers 103in its respective hole in the collection member, and thus the volume ofeach of the corresponding cavities 107. The graduations on cylinder 121are configured, in this example, to demark pre-set collection cavityvolumes. For example, the horizontal demarcations on cylinder 121indicate collection cavity volumes in a linear format; e.g. 0.1, 0.2,0.3, and so on, up to 1.0 cm³ of powder.

As mentioned, resin handler 100 is used to collect and dispense all or asub-set of 96 measured quantities of a powdered material. Referring toFIG. 5, resin handler 100 includes a plurality of valves 135 withinmanifold 105. Valves, 135, control fluid communication between thevacuum or positive pressure source (via the controller and itscorresponding valves) and manifold 105. In this example, each column of8 (versus rows of 12) collection cavities 107 is in fluid communicationwith a separate plenum 137 via two valves 135 (one at each end of thecolumn's corresponding manifold chamber). In this example there are 24valves 135, two for each column of eight collection cavities 107 (andeach column's corresponding plenum). Fluid communication between thevacuum or positive pressure source and each plenum 137 is terminated viaits two corresponding valves 135. Each valve 135 is adjusted, in thiscase turned, via a slot, 139, in its head. See FIG. 3. Thus, appropriateadjustment of valves 135 allows all or a subset of collection cavities107 to be used to collect and dispense a powdered material.

One skilled in the art would recognize that other configurations ofmanifolds and similar mechanisms fall within the scope of the invention.For example, manifold 105 could be valved such that any combination ofrows and columns in a matrix of collection cavities can be used tocollect and dispense a powder material. As well, the plurality ofcollection cavities can be positioned in any number of ordered (e.g.concentric rows) or random arrays, either aligned in a single plane asin this example, or out of plane with each other, such as a staggeredvertical arrangement such as on a curved surface of a collection member.

As mentioned, resin handler 100 is an example of a hand held apparatusof the invention. Another aspect of the invention is a supply bin forholding a powdered material that is collected and dispensed using, forexample, resin handler 100. FIG. 8A is a perspective of such a supplybin, 146, of the invention. Supply bin 146 includes a powdercompartment, 149, sized and shaped to accommodate a supply of thepowdered material and the collection member when collecting the powderedmaterial in collection cavities 107. For example, resin handler 100 ispositioned in the supply of powdered material, and the powdered materialis collected via vacuum into all or a subset of collection cavities 107.Preferably all of the desired collection cavities are filledsimultaneously, for example with the single push of switch 127.

In some cases, a portion of the powdered material protrudes beyond theaperture of collection cavities during collection due to for example thevacuum applied to the collection cavities. Supply bin 146 includes asqueegee, 153, configured to remove at least a portion of the powderedmaterial that protrudes beyond the aperture of each of the collectioncavities, when the collection cavities and the squeegee are moved acrossone another. Preferably this is done in a motion that allows the removedportions of the powder to fall back into powder compartment 149. Supplybin 146 also includes a powder catch compartment, 151, configured tocatch any of the powdered material that does not fall back into thepowder compartment when the collection cavities and the squeegee aremoved across one another.

FIG. 8B depicts a lid, 159, for supply bin 146. Supply bin 146 includesguides 155 for receiving lid 159, and a stop 157, both to ensure properalignment when lid 159 is engaged with supply bin 146. Lid 159 isparticularly useful when using powdered material that is hygroscopic.Preferably lid 159 and supply bin 146 form a substantially fluid-tightseal when engaged. One skilled in the art would understand thatformation of such a fluid-tight seal may include use of a sealingmember, such as a gasket (not shown). Supply bin 146 may also include amechanism for removing air from the interior of the bin when lid 159 isin place. Such a mechanism preferably includes mechanisms for applying avacuum to the interior of the closed supply bin or passing an inert gasthrough the interior volume to displace any air and/or moisture therein.Automated resin handling systems of the invention, as described above,preferably have the resin handler and supply bin in a self-containedcontrolled atmosphere environment. In one example, such an automatedsystem includes a forced air ventilation system to remove any airborneparticles and or volatile chemicals associated with applications forwhich the powdered material is needed, such as chemical synthesis inparallel. As such automated resin handling systems of the invention canbe part of a larger system, for example a parallel synthesizer. In aparticularly preferred embodiment, resin handlers of the invention aremodular components of a larger synthesis or assay system.

As mentioned, another aspect of the invention is method of collectingand dispensing a powdered material. FIG. 9 is a flowchart depictingaspects of a method, 200, of the invention. Method 200 starts withcollecting, substantially simultaneously, a plurality of measuredquantities of the powdered material in a plurality of collectioncavities, wherein each of the plurality of collection cavities is influid communication with, via an inlet within each cavity, a vacuumsource. See block 201. One skilled in the art would understand thatcollection of the powdered material into the cavities may occur withfinite variation in timing. That is, in some instances depending uponmechanical limitations or choice, each of the plurality of measuredquantities of the powdered material may be collected sequentially orrandomly, wherein the timing of each collection varies only by a verysmall amount of time such as a fraction of a second. For reasons ofthroughput, it is preferable to collect the plurality of measuredquantities of the powdered material simultaneously, although sequentialcollections, for example collecting 96 samples in a very short period oftime (on the order of seconds or a fraction of a second) do not escapethe scope of the invention.

Preferably each of the plurality of collection cavities includes afilter (as described above) to substantially prevent the powderedmaterial from entering the inlet. Preferably the filter is capable ofexcluding particles with an average particle size of between about 1 μmand 1000 μm, more preferably between about 1 μm and 500 μm, and mostpreferably between about 10 μm and 500 μm.

In some embodiments, the volume of each of the plurality of collectioncavities is dynamically adjusted during collection. That is, withcertain powders, it is advantageous to increase the volume (up to adesired volume) of each of the collection cavities during collection.One scenario where this is advantageous is when the particle diameter ofthe powdered material is of sufficient magnitude that one or moreparticles can lodge in the cavity and block further entry of particles.If the collection cavity volume is dynamically adjusted duringcollection (as described above), it helps to ensure that the powderedmaterial is collected in the cavity starting at what will be theinnermost surface of the cavity, e.g. the face of a plunger as describedabove, and incrementally stacked as the volume of the cavity isincreased, without blockage during collection. Preferably each of theplurality of collection cavities is capable of holding between about0.005 cm³ and 2 cm³ of the powdered material, more preferably betweenabout 0.01 cm³ and 1 cm³ of the powdered material, and most preferablybetween about 0.1 cm³ and 0.5 cm³ of the powdered material.

As mentioned above, in some embodiments it is desirable to collectvarying amounts of a powdered substance in each of the collectioncavities, for example, when the powder is a reagent used for abiological assay or chemical synthesis and the amount of powder neededto reach a certain reaction kinetic or carry out a particularstoichimetric conversion is to be studied. In these cases it isdesirable to have a system (as described above) or method that providesdynamically adjustable collection cavities. Methods of the inventionalso allow such variation in collection volume. For example, when thevolume of the collection cavities is held constant, methods of theinvention include collecting, substantially simultaneously, theplurality of measured quantities of the powdered material by varying thevacuum applied to each of the cavities, rather than using varying cavityvolume and filling the cavities to capacity as described above. In oneexample, the vacuum applied to the collection cavities is varied acrossa matrix of cavities (as in resin handler 100) by establishing a vacuumgradient among the cavities. In one example, this is done by choice ofmanifold design and/or configuration of fluid communication of thevacuum source with the manifold. For example, if fluid communicationbetween manifold 105 (see FIGS. 1-7) and a vacuum source is establishedappropriately, for example from a single source line at one end of themanifold, then a vacuum gradient may be generated that will collectsmaller amounts of powder in collection cavities further from the vacuumsource inlet in the manifold than those cavities in closer proximity tothe vacuum source inlet. Depending on the powder being collected, thevacuum, depth of cavities, etc., varying measured amounts of the powderare collected to make up the plurality of measured quantities of thepowdered material as described in FIG. 9, block 201.

Preferably the plurality of collection cavities are configured on acollection member such that when the collection member is registeredwith a multi-well vessel, each cavity of the plurality of collectioncavities is configured to dispense its corresponding quantity, of theplurality of measured quantities of powdered material, to acorresponding well of the multi-well vessel. Preferably the multi-wellvessel includes at least one of a 96-well format vessel, a 384-wellformat vessel, and a 1536-well format vessel.

Once the plurality of measured quantities of the powdered material arecollected, it may be preferable to move a squeegee and the aperture ofeach of the plurality of collection cavities across each other, toremove at least a portion of the powdered material that protrudes beyondthe aperture of each of the plurality of collection cavities. See block203. For powders of small average particle size, and depending on thevacuum applied, a typically conical portion of the powder will protrudebeyond at least some of the apertures of the collection cavities. Forobtaining consistency in the weight of each measured quantity, removingthe portions that protrude beyond the apertures as described ispreferable, although not necessary. Preferably the portion of thepowdered material that is removed, by moving the squeegee and theaperture of each of the plurality of collection cavities across eachother, is collected for reuse.

After the plurality of measured quantities are collected and anyunwanted material removed via squeegee, the measured quantities aredispensed. See block 205. Preferably dispensing the measured quantitiesis done substantially simultaneously, by terminating fluid communicationbetween each of the plurality of collection cavities and the vacuumsource while each of the plurality of collection cavities is orientedsuch that gravity pulls each of the plurality of measured quantities ofthe powdered material out of each of the plurality of collectioncavities. In addition, or alternatively, dispensing the powderedmaterial may include a positive pressure push of a gas (typically air,but in some cases preferably an inert gas) or a physical push via, forexample, a plunger as described above. After the measured quantities ofthe powdered material are dispensed, the method is done.

In some embodiments only a sub-set of the plurality of collectioncavities are used to collect and dispense the powdered material. In apreferred embodiment, the plurality of collection cavities are arrangedin a matrix, and the sub-set includes one or more rows, one or morecolumns, or combinations thereof of the matrix.

As described above, one way of performing methods of the invention isusing a hand-held unit that includes the plurality of collectioncavities. Also preferable is using an automated mechanism configured tocollect the powdered material in all or the sub-set of the plurality ofcollection cavities, move the aperture of each of the plurality ofcollection cavities and the squeegee across one another, and delivereach of the plurality of measured quantities of the powdered solid, viathe plurality of collection cavities, to a plurality of vesselscorresponding to all or the sub-set of the plurality of collectioncavities containing the powdered material. This is particularly true invery high-throughput environments such as automated combinatorialchemistry or biological screening.

While this invention has been described in terms of a few preferredembodiments, it should not be limited to the specifics presented above.Many variations on the above-described preferred embodiments, can beemployed. Therefore, the invention should be broadly interpreted withreference to the following claims.

1. An apparatus for automatically collecting, substantially simultaneously, a plurality of measured quantities of a powdered material and dispensing, substantially simultaneously, each of the plurality of measured quantities of the powdered material, the apparatus comprising: (a) a plurality of collection cavities, each of said collection cavities comprising an inlet for fluid communication therein and a filter configured to prevent the powdered material from entering; (b) a vacuum source, said vacuum source connected to each of the plurality of collection cavities via the inlet therein; and (c) a control valve configured to establish or terminate fluid communication between the vacuum source and each of the plurality of collection cavities.
 2. The apparatus of claim 1, wherein the volume of each of the plurality of collection cavities is dynamically adjustable.
 3. The apparatus of claim 2, wherein the plurality of collection cavities are configured on a collection member such that when the collection member is registered with a multi-well vessel, each cavity of the plurality of collection cavities is positioned to dispense its corresponding quantity, of the plurality of measured quantities of the powdered material, into a corresponding well of the multi-well vessel.
 4. The apparatus of claim 3, wherein the multi-well vessel comprises at least one of an 8-well format vessel, a 24-well format vessel, a 96-well format vessel, a 384-well format vessel, and a 1536-well format vessel.
 5. The apparatus of claim 2, wherein each of the plurality of collection cavities is capable of holding between about 0.005 cm³ and 2 cm³ of the powdered material.
 6. The apparatus of claim 2, wherein each of the plurality of collection cavities is capable of holding between about 0.01 cm³ and 1 cm³ of the powdered material.
 7. The apparatus of claim 2, wherein each of the plurality of collection cavities is capable of holding between about 0.1 cm³ and 0.5 cm³ of the powdered material.
 8. The apparatus of claim 3, wherein said collection member comprises: (i) a plurality of holes, said plurality of holes slidably engage-able with; (ii) a plurality of plungers, each of said plurality of plungers comprising a tube, open at both ends, said filter affixed at the end of the tube that comes in proximity to the powdered material during collection and the other end of the tube in fluid communication with the vacuum source; wherein the volume of each of the plurality of collection cavities is defined substantially by the volume from the aperture of its corresponding hole to the face of its corresponding plunger.
 9. The apparatus of claim 8, wherein the filter is capable of excluding particles with an average particle size of between about 1 μm and 1000 μm.
 10. The apparatus of claim 9, wherein the filter is capable of excluding particles with an average particle size of between about 1 μm and 500 μm.
 11. The apparatus of claim 9, wherein the filter is capable of excluding particles with an average particle size of between about 10 μm and 500 μm.
 12. The apparatus of claim 9, wherein the filter comprises at least one of a semi-rigid screen, a sieve, a collection of micro-tubes, a perforated ceramic, a perforated plastic, a perforated glass, a porous cermet, and a porous metal.
 13. The apparatus of claim 9, wherein the plurality of plungers are affixed to and in fluid communication with a manifold, said manifold serving to establish fluid communication between each of the plurality of plungers and the vacuum source.
 14. The apparatus of claim 13, wherein the manifold further comprises a plurality of valves, said plurality of valves configured such that fluid communication between the vacuum source and all or a sub-set of the plurality of collection cavities can be shut off.
 15. The apparatus of claim 14, wherein the plurality of collection cavities are arranged in a matrix, and the sub-set comprises one or more rows, one or more columns, or combinations thereof of said matrix.
 16. The apparatus of claim 13, wherein the relative position of each plunger within its corresponding hole is established by an adjustment mechanism configured to vary the distance between the manifold and the collection member.
 17. The apparatus of claim 16, wherein each plunger is capable of displacing each of the plurality of measured quantities of the powdered material from the corresponding hole wherein said each plunger resides.
 18. The apparatus of claim 16, wherein the adjustment mechanism comprises at least one of a lead screw and a pneumatic cylinder.
 19. The apparatus of claim 14, further comprising a controller, said controller comprising: (a) a plurality of solenoids for controlling the control valve and said plurality of valves; (b) the vacuum source; (c) a positive pressure source for delivering a positive pressure of a gas; and (d) an associated logic configured to automatically control the plurality of solenoids based on a manual switch control, a pre-programmed algorithm, or both; wherein the control valve, the plurality of valves, and combinations there of are used to control fluid communication between each of the collection cavities, via their respective inlets, and either the vacuum source or the positive pressure source.
 20. The apparatus of claim 19, wherein the vacuum source is capable of producing both a high vacuum and a low vacuum, and the positive pressure source is capable of delivering both a high-pressure flow of the gas and a low-pressure flow of the gas.
 21. The apparatus of claim 20, wherein the gas comprises at least one of air and an inert gas.
 22. The apparatus of claims 19, further comprising a supply bin for holding the powdered material, said supply bin comprising: (a) a powder compartment sized and shaped to accommodate a supply of the powdered material and the collection member when collecting the powdered material in the plurality of collection cavities therein; and (b) a squeegee configured to remove at least a portion of the powdered material that protrudes beyond the aperture of each of the plurality of collection cavities, during collection, when the aperture of each of the plurality of collection cavities and the squeegee are moved across one another.
 23. The apparatus of claim 22, configured such that the portion of the powdered material that protrudes beyond the aperture of each of the plurality of collection cavities, after removed by said squeegee, is returned into the powder compartment.
 24. The apparatus of claim 23, further comprising a powder catch compartment configured to catch any of the powdered material that does not fall back into the powder compartment when the aperture of each of the plurality of collection cavities and the squeegee are moved across one another.
 25. The apparatus of claim 19, wherein the collection member, the manifold, and the manual switch control are combined in a hand-held unit, said hand-held unit in electrical and fluid communication with the controller.
 26. The apparatus of claim 19, further comprising an automated mechanism configured to collect the powdered material in all or the sub-set of the plurality of collection cavities, move the aperture of each of the plurality of collection cavities and the squeegee across one another, and deliver each of the plurality of measured quantities of the powdered solid, via the plurality of collection cavities, to a plurality of vessels corresponding to all or the sub-set of the plurality of collection cavities containing the powdered material.
 27. The apparatus of claim 3, wherein at least one of the collection member and each of the plurality of collection cavities comprise an anti-static material.
 28. The apparatus of claim 27, wherein the anti-static material comprises at least one of a plastic, a metal, a glass, and a ceramic.
 29. The apparatus of claim 8, wherein the collection member further comprises a plurality of guides, each guide of said plurality of guides residing at the aperture of each of the plurality of collection cavities, each guide of said plurality of guides configured to aide in registration of its corresponding collection cavity with a receiving vessel.
 30. The apparatus of claim 29, wherein the collection member further comprises an alignment guide, said alignment guide configured to aide in registration of the collection member with the multi-well vessel.
 31. The apparatus of claim 5, capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.1 cm³.
 32. The apparatus of claim 5, capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.005 cm³.
 33. The apparatus of claim 5, capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.001 cm³.
 34. A method of collecting and dispensing a powdered material, the method comprising: (a) collecting, substantially simultaneously, a plurality of measured quantities of the powdered material in a plurality of collection cavities, wherein each of said plurality of collection cavities is in fluid communication with, via an inlet within each cavity, a vacuum source; and (b) dispensing, substantially simultaneously, the plurality of measured quantities of the powdered material by terminating, substantially simultaneously, fluid communication between each of said plurality of collection cavities and the vacuum source while each of the plurality of collection cavities is oriented such that gravity pulls each of the plurality of measured quantities of the powdered material out of each of the plurality of collection cavities; wherein each of the plurality of collection cavities comprises a filter to substantially prevent said powdered material from entering its corresponding inlet.
 35. The method of claim 34, wherein the volume of each of the plurality of collection cavities is dynamically adjusted during (a).
 36. The method of claim 34, further comprising applying a positive pressure of a gas to each of said collection cavities, via the inlet within each cavity, to facilitate removal of each of the plurality of measured quantities of the powdered material therein.
 37. The method of claim 36, wherein the gas comprises at least one of air and an inert gas.
 38. The method of claim 34, wherein the plurality of collection cavities are configured on a collection member such that when the collection member is registered with a multi-well vessel, each cavity of the plurality of collection cavities is configured to dispense its corresponding quantity, of the plurality of measured quantities of powdered material, to a corresponding well of the multi-well vessel.
 39. The method of claim 38, wherein the multi-well vessel comprises at least one of an 8-well format vessel, a 24-well format vessel, a 96-well format vessel, a 384-well format vessel, and a 1536-well format vessel.
 40. The method of claim 34, wherein each of the plurality of collection cavities is capable of holding between about 0.005 cm³ and 2 cm³ of the powdered material.
 41. The method of claim 34, wherein each of the plurality of collection cavities is capable of holding between about 0.01 cm³ and 1 cm³.
 42. The method of claim 34, wherein each of the plurality of collection cavities is capable of holding between about 0.1 cm³ and 0.5 cm³ of the powdered material.
 43. The method of claim 34, wherein the filter is capable of excluding particles with an average particle size of between about 1 μm and 1000 μm.
 44. The method of claim 34, wherein the filter is capable of excluding particles with an average particle size of between about 1 μm and 500 μm.
 45. The method of claim 34, wherein the filter is capable of excluding particles with an average particle size of between about 10 μm and 500 μm.
 46. The method of claim 34, wherein a sub-set of the plurality of collection cavities are used to collect the powdered material during (a) and dispense the powdered material during (b).
 47. The method of claim 46, wherein the plurality of collection cavities are arranged in a matrix, and the sub-set comprises one or more rows, one or more columns, or combinations thereof of the matrix.
 48. The method of claim 34, further comprising moving a squeegee and the aperture of each of the plurality of collection cavities across each other, to remove at least a portion of the powdered material that protrudes beyond the aperture of each of the plurality of collection cavities, after (a) and before (b).
 49. The method of claim 48, wherein the portion of the powdered material that is removed, by moving the squeegee and the aperture of each of the plurality of collection cavities across each other, is collected for reuse.
 50. The method of claim 48, performed using a hand-held unit, said hand held unit comprising the plurality of collection cavities.
 51. The method of claim 48, performed using an automated mechanism configured to collect the powdered material in all or the sub-set of the plurality of collection cavities, move the aperture of each of the plurality of collection cavities and the squeegee across one another, and deliver each of the plurality of measured quantities of the powdered solid, via the plurality of collection cavities, to a plurality of vessels corresponding to all or the sub-set of the plurality of collection cavities containing the powdered material.
 52. The method of claim 40, wherein each of the plurality of collection cavities is capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.1 cm³.
 53. The method of claim 40, wherein each of the plurality of collection cavities is capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.005 cm³.
 54. The method of claim 40, wherein each of the plurality of collection cavities is capable of collecting each of the plurality of measured quantities of the powdered material to within about ±0.001 cm³.
 55. The method of claim 40, wherein the plurality of collection cavities is formed via deformation of a flexible membrane into a plurality of deformation cavities via at least a partial vacuum applied via each of said plurality of deformation cavities.
 56. The method of claim 55, wherein said flexible membrane deforms to conform to interior surface of each of said plurality of deformation cavities, whereby the volume of each of said plurality of deformation cavities substantially defines the volume of the powdered material collected in the corresponding collection cavity formed therein.
 57. The method of claim 55, wherein said flexible membrane deforms, but does not conform to the interior surface of each of said plurality of deformation cavities, whereby the volume of each of said plurality of collection cavities is defined substantially by the volume of the depression formed in the flexible membrane caused by deformation of said flexible membrane.
 58. The method of claim 55, wherein upon release of said at least partial vacuum the flexible membrane reforms substantially to the shape it possessed prior to application of said at least partial vacuum, thereby expelling each of the individual quantities of the powdered material collected. 